Effect of verapamil on malignant tissue blood flow in SMT-2A tumor-bearing rats.

We investigated the influence of the calcium antagonist verapamil on malignant and normal tissue blood flow using 25-micrometer 113Sn-labeled microspheres. Isogeneic Wistar-Furth rats were inoculated with a metastasizing mammary gland adenocarcinoma (SMT-2A) in the hindlimb musculature and mammary gland. Verapamil was administered as an i.v. bolus via an external jugular vein catheter followed by a supplemental constant infusion with a Harvard infusion pump. Plasma verapamil levels were determined by high performance liquid chromatography, and heart rate and systemic blood pressure were monitored. Verapamil in concentrations of 100 to 200 ng/ml resulted in an approximate 50% increase in tumor blood flow compared to control levels (p less than 0.001) regardless of the site of tumor implantation. These levels were not associated with a significant alteration in arterial blood pressure. These data suggest that verapamil in concentrations currently used in humans may provide a means of improving the delivery of chemotherapeutic agents to solid neoplasms and may also enhance the effectiveness of ionizing radiation treatment by increasing tumor oxygenation.